关键词: Desvenlafaxine Intoxication LC–MS/MS Paroxetine

Mesh : Humans Desvenlafaxine Succinate / blood Paroxetine / blood Female Adult Tandem Mass Spectrometry / methods Drug Overdose Chromatography, Liquid / methods Solid Phase Extraction / methods Fatal Outcome Antidepressive Agents / poisoning blood Limit of Detection Selective Serotonin Reuptake Inhibitors / poisoning blood analysis

来  源:   DOI:10.1016/j.jpba.2024.116148

Abstract:
Desvenlafaxine (O-desmethylvenlafaxine) and paroxetine are antidepressants that inhibit serotonin reuptake. Despite their relatively safe profiles, several serious side effects, including serotonin syndrome, bleeding, mania, and high blood pressure, are observed. We report the confirmation of the death of a 41-year-old female, with an overdose of desvenlafaxine and paroxetine suspected as the main cause of death. To quantify the level of desvenlafaxine and paroxetine in whole blood and urine, solid phase extraction combined with liquid chromatography-tandem mass spectrometry was developed and validated. Calibration curves were linear with coefficients of determination (r2) >0.999 for desvenlafaxine and paroxetine. The limits of detection and the limits of quantification for both desvenlafaxine and paroxetine were 0.001 µg/mL and 0.02 µg/mL, respectively. Desvenlafaxine and paroxetine were detected in the postmortem samples, along with various psychiatric drugs, and the blood alcohol content level was below 0.010%. The concentrations of desvenlafaxine and paroxetine in the heart blood were 11.0 µg/mL and 2.1 µg/mL, respectively, indicating lethal concentrations. In the urine, the concentrations of desvenlafaxine and paroxetine were 87.7 µg/mL and 3.5 µg/mL, respectively. This is the first report to determine the blood concentration of desvenlafaxine in a fatal intoxication caused by an overdose of desvenlafaxine single formulation.
摘要:
去文拉法辛(O-去甲基文拉法辛)和帕罗西汀是抑制5-羟色胺再摄取的抗抑郁药。尽管他们的个人资料相对安全,几个严重的副作用,包括5-羟色胺综合征,出血,躁狂症,还有高血压,被观察到。我们报告了一名41岁女性死亡的确认,怀疑过量服用去文拉法辛和帕罗西汀是主要死亡原因。为了量化全血和尿液中的去文拉法辛和帕罗西汀的水平,建立了固相萃取-液相色谱-串联质谱联用技术,并进行了验证。去文拉法辛和帕罗西汀的校准曲线与测定系数(r2)>0.999呈线性关系。去文拉法辛和帕罗西汀的检测限和定量限分别为0.001µg/mL和0.02µg/mL,分别。在尸检样本中检测到去文拉法辛和帕罗西汀,以及各种精神药物,血液酒精含量低于0.010%。心脏血液中去文拉法辛和帕罗西汀的浓度分别为11.0µg/mL和2.1µg/mL,分别,表明致死浓度。在尿液中,去文拉法辛和帕罗西汀的浓度分别为87.7µg/mL和3.5µg/mL,分别。这是确定在过量使用去甲文拉法辛单一制剂引起的致命中毒中去甲文拉法辛血液浓度的第一份报告。
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